Disclosed herein are devices and methods of making and using devices for sublimation. In one embodiment, an apparatus for performing sublimation is disclosed. The apparatus includes a lower assembly with a heat source, an upper assembly with a heat exchange core, and a hinge assembly mechanically coupling the lower assembly to the upper assembly. The apparatus is configured for allowing a substrate to be positioned within an interior chamber of the upper assembly when in an open position, facilitating deposition of a material onto the substrate via sublimation when in a closed position, and allowing removal of the substrate with the material when returned to the open position.
Legal claims defining the scope of protection, as filed with the USPTO.
a lower assembly; an upper assembly; allowing a substrate to be positioned within an interior chamber when in an open position; facilitating deposition of a material onto the substrate via sublimation when in a closed position; and allowing removal of the substrate with the material when returned to the open position. a hinge assembly mechanically coupling the lower assembly to the upper assembly, wherein the apparatus is configured for: . An apparatus for providing sublimation, the apparatus comprises:
claim 1 . The apparatus of, wherein the substrate is used in sample preparation for mass spectrometry imaging.
claim 1 . The apparatus of, wherein the lower assembly comprises a vacuum inlet configured for attachment to a vacuum pump.
claim 3 . The apparatus of, wherein the lower assembly further comprises a heat source electrically coupled via an electrical interconnect.
claim 4 . The apparatus of, wherein the upper assembly is configured to provide an internal chamber when in the closed position and comprises a sample holder.
claim 5 . The apparatus of, wherein the internal chamber is approximately a shape of a cylinder.
claim 5 . The apparatus of, wherein the internal chamber is approximately a shape of at least one of a prism, a sphere, and a cone.
claim 5 . The apparatus of, wherein the sample holder is configured to hold a plurality of samples.
claim 5 . The apparatus of, where samples are secured directly to a heat exchange core.
claim 9 . The apparatus of, wherein a magnetic mask is used to secure the samples to the heat exchange core.
claim 5 . The apparatus of, wherein the upper assembly further comprises a heat exchange core.
claim 11 . The apparatus of, wherein the heat exchange core is an isolated solid metal block extending from the internal chamber to an exterior of the upper assembly and acts as a heat sink when cooled with various coolants.
claim 12 . The apparatus of, wherein the heat exchange core is configured to be thermally coupled with a thermoelectric cooler.
claim 13 . The apparatus of, wherein the heat exchange core is configured to be thermally coupled with a liquid coolant, allowing cold temperatures below zero Celsius.
claim 14 . The apparatus ofwherein the liquid coolant can cool the heat exchange core to temperatures below negative 60 Celsius.
claim 5 . The apparatus of, wherein a removeable funnel is positioned inside the interior chamber to direct matrix particle cloud evenly towards a sample.
claim 16 . The apparatus of, wherein the removeable funnel comprises at least one of a polymer resin and other insulative high heat plastics material onto which allow matrix crystals to form less quickly than on colder metal surfaces.
claim 5 . The apparatus of, wherein the lower assembly further comprises a removeable patterned template for holding a substance for sublimation.
claim 5 . The apparatus of, wherein the lower assembly further comprises a direct contact plate for holding a substance for sublimation.
claim 19 . The apparatus of, wherein the direct contact plate has a patterned surface to promote even matrix distribution.
claim 19 . The apparatus of, wherein the direct contact plate is in direct contact with the heat source for holding matrix to be heated via the heat source during sublimation.
claim 5 . The apparatus of, wherein the heat source is an infrared heater configured to heat the interior chamber through a non-metallic porthole.
claim 5 . The apparatus of, wherein the heat source is a ceramic heater configured to heat the interior chamber to a temperature of at least 300 degrees Celsius.
claim 5 . The apparatus of, wherein the heat source is configured to achieve a temperature setpoint in less than 120 seconds.
claim 1 . The apparatus of, wherein the hinge assembly comprises a motor mechanism for automatically transitioning the apparatus between the open position and the closed position.
claim 1 . The apparatus of, wherein the interior chamber has a volume less than one liter and a sample capacity of up to four microscope slides.
claim 1 . The apparatus of, wherein the interior chamber has a volume and sample area has at or less than a ratio of 1:7500 liters to square millimeters.
configuring the apparatus to be in an open position; positioning a substrate within an interior chamber of the apparatus; configuring the apparatus to be in a closed position; and adjusting a pressure and temperatures of the interior chamber for sublimation of a material onto the substrate; configuring the apparatus to be in the open position; and removing the substrate from the interior chamber of the apparatus. . A method of operating an apparatus for providing sublimation, the method comprising:
mechanically assembling a lower assembly; mechanically assembling an upper assembly; and allowing a substrate to be positioned within an interior chamber when in an open position; facilitating deposition of a material onto the substrate via sublimation when in a closed position; and allowing removal of the substrate with the material when returned to the open position. mechanically coupling the lower assembly to the upper assembly using a hinge assembly, wherein the apparatus is configured for: . A method of manufacturing an apparatus configured for sublimation, the method comprising:
Complete technical specification and implementation details from the patent document.
This application claims priority to U.S. Provisional Application No. 63/710,838, titled “SUBLIMATION APPARATUSES AND METHODS OF MAKING AND USING THE SAME,” filed Oct. 23, 2024, the entire content of which is hereby incorporated by reference herein.
This disclosure generally relates to the deposition of chemicals onto a substrate via sublimation. More specifically, apparatuses are disclosed for sample preparation for mass spectrometry imaging. Additionally, methods of making and using the apparatuses are also disclosed.
While various spray assemblies have been developed for coating a planar surface, the desire for enhanced quantitative and qualitative controls of chemical deposition continues to exist. Sublimation deposition offers an improved alternative to spraying. Sublimation is the conversion of a substance directly from a solid state to a gaseous state or from a gaseous state to a solid state without becoming a liquid. Each substance has conditions for sublimation that can occur with a specific pressure and temperature relationship. Commonly, vacuum levels of pressure are used for sublimation to occur, as this lowers the temperature necessary to achieve sublimation of a substance. Sublimation is possible with many substances under the correct vapor pressure and temperature relationships. A use of sublimation is to avoid the transition of a substance to a liquid where the presence of a liquid can have an impact on the results. For example, sublimation (from gaseous state to solid state) can provide a better alternative to spraying (from liquid to solid state) a material on to a substrate to achieve a more uniform coating.
As such, improved devices and methods are needed to perform a variety of applications for sublimation.
This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.
Disclosed herein are devices and methods of making and using devices for sublimation. In one embodiment, an apparatus for providing sublimation is disclosed. The apparatus includes a lower assembly, an upper assembly, and a hinge assembly mechanically coupling the lower assembly to the upper assembly. The apparatus is configured for allowing a substrate to be positioned within an interior chamber when in an open position, facilitating deposition of a material onto the substrate via sublimation when in a closed position, and allowing removal of the substrate with the material when returned to the open position.
In another embodiment, a method for operating an apparatus for providing sublimation is disclosed. The method includes configuring the apparatus to be in an open position and positioning a substrate within an interior chamber of the apparatus. The method further includes configuring the apparatus to be in a closed position with the substrate within the interior chamber and adjusting a pressure and a temperature of the interior chamber for sublimation of a material onto the substrate. The method still further includes configuring the apparatus to be in the open position and removing the substrate from the interior chamber of the apparatus.
In another embodiment, a method of manufacturing an apparatus for providing sublimation is disclosed. The method includes mechanically assembling a lower assembly, mechanically assembling an upper assembly, mechanically coupling the lower assembly to the upper assembly using a hinge assembly. The apparatus is configured for allowing a substrate to be positioned within an interior chamber when in an open position, facilitating deposition of a material onto the substrate via sublimation when in a closed position, and allowing removal of the substrate with the material when returned to the open position.
The presently disclosed subject matter is described with specificity to meet statutory requirements. However, the description itself is not intended to limit the scope of this patent. Rather, the inventors have contemplated that the claimed invention might also be embodied in other ways, to include different steps or elements similar to the ones described in this document, in conjunction with other present or future technologies. Moreover, although the term “step” may be used herein to connote different aspects of methods employed, the term should not be interpreted as implying any particular order among or between various steps herein disclosed unless and except when the order of individual steps is explicitly described.
Disclosed herein are devices and methods of making and using devices for chemical deposition onto a substrate via sublimation. More specifically, the sublimation may be used for sample preparation for mass spectrometry imaging. Further this chemical deposition may be used for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). Mass spectrometry imaging is a technique for the spatial analysis of analytes within samples, such as the distribution of drugs, lipids, metabolites, proteins, peptides and other small molecules. The quality of the spatial analysis can be related to the quality of the matrix deposition onto a substrate, and in particular to the matrix crystal sizes that are formed during deposition.
Sublimation, as described, is a technique that can be employed to deposit MALDI matrix onto a substrate with the potential for small crystal sizes due to the lack of liquid used in the process. This process requires the use of vacuum and temperature gradient to move the matrix chemicals onto the substrate/sample. For example, an underlying substance or layer can be a substrate. In the technical field of this application, samples are commonly glass microscope slides or metal target plates containing biological material such as tissues or cells. The ability to control the temperature gradient via both matrix heating and sample cooling improves the quality and reproducibility of matrix deposition for MALDI MSI analysis. In addition, the ability to deposit matrix across a larger area/more samples improve the throughput of this technique in laboratories.
1 FIG. 1 FIG. 1 FIG. 100 102 104 102 104 106 102 108 104 102 110 112 110 114 116 116 116 104 118 118 104 120 120 depicts a mechanical diagramillustrating an open position for one embodiment of an apparatus for sublimation including a lower assemblyand an upper assemblyin accordance with embodiments of the present disclosure. The apparatus includes a lower assemblyand an upper assemblymechanically coupled via a hinge assembly. The lower assemblyincludes a vacuum inletconfigured for attachment to a vacuum pump, alternatively the upper assemblycould include a vacuum inlet. The lower assemblyfurther includes a plurality of sensors (not shown in) accessible via an electrical interconnect. The lower assembly also includes a heat sourcethat is electrically coupled via the electrical interconnect. The lower assembly further includes a labeland a plurality of non-skid feetA-D (non-skid footD is not shown in). The upper assemblyincludes a handlefor configuring the apparatus in one of an open state or a closed state. Alternately, the hinge assembly may include a motor mechanism for automatically transitioning the apparatus between the open position and the closed position without the need for the handle. The upper assemblyis configured to provide an internal chamber and includes a sample holder. The sample holderis configured to hold a plurality of slides (e.g., glass microscope slides) or one of more metal target plates for matrix sublimation.
2 FIG. 1 FIG. 200 104 202 202 202 202 depicts a mechanical diagramillustrating a closed position of the apparatus ofin accordance with embodiments of the present disclosure. The upper assemblyincludes a heat exchange core. The heat exchange coremay be an isolated solid metal block extending from the interior chamber to the exterior and acts as a heat sink when cooled with various coolants. Additionally, the heat exchange coremay be configured to be thermally coupled with a thermoelectric cooler (e.g., a Peltier cooler). Alternately, the heat exchange coremay be configured to be thermally coupled with an external heatsink configured for force air heat transfer (e.g., a fan) or with the various liquid coolants via a separate radiator assembly.
3 FIG. 1 FIG. 3 FIG. 300 102 102 302 302 304 304 112 102 112 102 306 112 402 102 depicts a mechanical diagramillustrating a cut away side view of the lower assemblyofin accordance with embodiments of the present disclosure. The lower assemblyincludes washersA-B and springsA-B that provide isolation of a bottom side of the heat sourcefrom the case of the lower assembly. Additional washers and springs (not shown in) provide additional thermal isolation and support for the bottom side of the heat sourcefrom the case of the lower assembly. The lower assembly also includes a gasketthat provides additional isolation of the top side of the heat sourcefrom the diffusing plateand the surrounding lower assembly.
4 FIG. 1 FIG. 400 112 402 102 402 102 112 404 404 402 102 depicts a mechanical diagramillustrating the lower assembly ofand further illustrating the heat sourceand a diffusing platewithin the lower assemblyin accordance with embodiments of the present disclosure. In this embodiment, the diffusing plateis a thin plate of metal fixed in the lower assemblyto hold the heat sourcein position and distribute air flow via gap. A gapisolates the diffusing platefrom the case of the lower assembly.
5 FIG. 1 FIG. 500 502 102 112 502 502 112 502 112 depicts a mechanical diagramillustrating some embodiments of the apparatus where a direct contact platepositioned in the lower assemblyand above the heat sourceofin accordance with embodiments of the present disclosure. The direct contact plateis a fixed vessel for holding matrix to be heated during sublimation. The direct contact plateis attached in direct contact with the heat source. A wafer may be used instead of the direct contact plate. The wafer is a removeable patterned template also containing matrix to be heated via the heat sourceduring sublimation.
6 FIG. 1 FIG. 600 104 104 602 104 202 604 104 202 104 606 604 depicts a mechanical diagramillustrating a cut away side view of the upper assemblyofin accordance with embodiments of the present disclosure. The upper assemblyfurther includes an O-ringfor maintaining vacuum and thermally isolating the case of the upper assemblyfrom the heat exchange core. Additionally, an air gapprovides further thermal isolation of the case of the upper assemblyfrom the heat exchange core. The upper assemblyfurther includes a drainfor removing or preventing condensation within the air gap
1 FIG. 6 FIG. The previously described apparatus ofthroughovercomes many limitations of currently available sublimation apparatuses including the issues described in the following paragraphs.
Issue one, the heat distribution source is limited in size (usually less than 2,000 square millimeters) preventing uniform coating of a large sample area/multiple substrates.
Issue two, the ultimate temperature of the heat source is limited due to the heater technology (e.g., heater cartridge, heater film, convection, etc.). The maximum temperature is typically limited to 250 degrees Celsius.
Issue three, the chamber lower assembly can become very hot requiring long cooling times before opening and resulting in possibly unsafe operation.
Issue four, uneven contact surfaces between heater and wafer can create space that under vacuum becomes a significant insulative barrier, thus limiting the ultimate temperature attained by the matrix.
Issue five, vacuum is typically pulled from the top of the chamber which creates a very cumbersome upper assembly that takes time to disconnect and move away from the lower assembly, reducing the speed and ease of retrieving the substrate and/or sample holder.
Issue six, vacuum draft can be substantial inside the chamber and a large matrix deposit layer may be deposited on the inside wall of the chamber.
Issue seven, wafer size is limited due to the size of the heater. In some cases a larger area of matrix coating is beneficial to allow the coating of more samples for higher throughput and more complete coverage to reduce edge effects.
Issue eight, cooling with liquid coolant typically requires additional tubing for either circulation of a cooled liquid for drainage of a melting solid/liquid mixture. Tubing adds complexity to use and requires additional space.
Issue nine, cooling at ultra-low temperatures (e.g., −78 degrees Celsius with dry ice/acetone mixture) creates issues with the upper assembly of sublimation chambers. When using glass for the fabrication of the chamber, temperature cycling between ambient and −78 degrees Celsius can cause accelerated cracking and failure. When using aluminum or other metal, the upper assembly and lower assembly can frost over due to the higher heat conductivity of metals.
Issue ten, the previously described frost can extend to connectors and electrical connections and reduce their lifespan. The frost also makes the assembly difficult to safely handle. This requires special gloves and extended temperature equilibration time to return to ambient temperature.
Issue eleven, distances as much as ten to twenty centimeters between heat source with matrix vessel and substrate (and sample holder) can lead to increased matrix consumption due to loss to surrounding surfaces.
1 FIG. 6 FIG. The previously described apparatus ofthroughand other similar embodiments offer many improvements over the above limitations. These improvements are described in the following paragraphs.
In general, the heat source has a surface area greater than 2,000 square millimeters, allowing for a large wafer or direct contact plate to be heated quickly and consistently. The larger size matrix vessel results in increased sample area for sublimation and increases the sample throughput. In the currently described embodiment, the heat source has a surface area greater than 10,000 square millimeters and the heat source is circular in shape. In other embodiments the heat source may be square or rectangular in shape and may vary in sizes smaller than 10,000 square millimeters.
In the currently described embodiment, the heat source is a ceramic heater capable of up to 400 degrees Celsius and can reach temperature setpoint in at or less than 120 seconds. Alternatively, the heat source may be an infrared heater, an induction heater, a resistance heater, and/or the like.
In the currently described embodiment, the heat source is suspended inside the chassis using spring loaded posts with small area contact points and high temperature polymer gaskets. Alternatively, the heat source may be infra-red, induction or other wave energy and maybe positioned outside the vacuum chamber and heat the matrix vessel through a high silica glass porthole or other non-metallic material that efficiently conducts heat without reaching melting point or unsafe temperatures.
In the currently described embodiment, the contact points are ceramic on ceramic.
In the currently described embodiment, the contact area is less than five percent of the heater surface area
In the currently described embodiment, high temperature polymer gaskets are capable of withstanding temperatures up to 400 degrees Celsius. By suspending the heat source heat transfer to the chassis is reduced. This minimizes heat loss and focuses the energy on the wafer or the direct contact plate. Additionally, the suspension of heat source via spring loaded posts extends the lifetime of heat source by allowing the material to expand and contract with heat cycles without external forces to the heater that may lead to cracking and failure.
In the currently described embodiment, the heater is positioned less than four centimeters from the sample holder. This distance limits the amount of matrix lost to the surrounding surfaces. Alternatively the heater could be positioned greater than four centimeters from the sample holder. The wafer or vessel containing matrix may be attached to the heat source for improved heat transfer. Additionally, the wafer may be connected with thermal paste to the heater. Clamps, screws, and/or brackets may also be used to secure the wafer or vessel against the heater
In the currently described embodiment, vacuum is pulled from a channel located in the lower assembly allowing all vacuum tubing, connector and gauges to stay in place during the opening of the chamber. A hinge and handle design is implemented for fast, easy and safe opening of the chamber, even before all surfaces have returned to ambient temperature.
In the currently described embodiment, the sublimation chamber has a volume of less than 0.8 liter with a sample area capacity of at or greater than 7,500 square millimeters for 4 microscope slides.
In the currently described embodiment, a diffusing plate is inserted between the vacuum inlet, the matrix vessel, and the heat source allowing a uniform vacuum pull and limiting the loss of significant amount of matrix powder. The resulting surface also acts as a mask that protects the inside compartment of the lower assembly.
In the currently described embodiment, the diffusing plate has a flower pattern, and the center of the plate is cut in the same shape as the wafer. The diffusing plate also positions the matrix wafer to ensure consistent placement of the removeable wafer on the heat source with every sublimation cycle.
In the currently described embodiment, a permanent direct contact plate may be substituted for the wafer as a vessel for holding matrix to potentially improve heat transfer. The direct contact plate is affixed in direct contact with the heat source and is made of metal. Alternately, the direct contact plate may be made of other heat conductive materials. Alternately, the direct contact plate may be circular, rectangular, or square in shape. The direct contact plate may be larger than the surface area of heat source for increased sample area of sublimation. In the currently described embodiment, the direct contact plate has a surface area that is approximately forty percent larger than heat source and wafer. The matrix may be applied to a template by spray or other deposition technique to create consumable matrix pads that can be deposited onto the direct contact plate. Alternately, the direct contact plate may have a patterned surface or discrete wells to promote even or selective distribution of matrix across its surface.
In the currently described embodiment, the upper assembly includes a heat exchange core that is embedded in the upper assembly but also insulated from the upper assembly, and therefore from the chassis. The heat exchange core extends from the interior of the chamber where it is in contact with the sample holder to the exterior of the chamber to be in contact with a coolant.
In the currently described embodiment, the upper assembly includes an aluminum block (i.e., heat exchange core) that is centered and held in place in the chassis with a polymer spacer capable of withstanding ultra-low temperature. The material may be an ultra high molecular weight (UHMW) polyethylene or the like. The heat exchange core does not make contact with the chassis but is maintained against a silicone O-ring that is compressed when the assembly is under vacuum. The heat exchange core may include magnets to hold the sample holder or sample mask.
In the currently described embodiment, the heat exchange core is circular in shape. Alternately the heat exchange core may be rectangular or square in shape.
In the currently described embodiment, the heat exchange core surface area is larger than the sample holder, with an area greater than 10,000 square millimeters. Alternately the heat exchange core may have a surface that is smaller than the sample holder or sample mask.
The heat exchange core may have the same surface area both interior and exterior to the chamber. Alternatively, the surface areas may be different.
In the currently described embodiment, the heat exchange core has a flat surface that provides improved conductivity with the external recipient containing the coolant. Alternately a textured surface may be used to increase this surface area. The coolant may be a cooled liquid such as ice water, dry ice with acetone, liquid nitrogen, a solid heat sink, a heat exchanger connected to an external chiller, or a powered cooling device (e.g., a Peltier cooler).
In the currently described embodiment, the heat transfer efficiency of the heat exchange core, and the fact that it is insulated from the bulkier chassis, allows for minimal heat loss. As such, the substrate retaining device maintains a temperature within plus or minus ten degrees Celsius of a coolant temperature.
In the currently described embodiment, locations around the heat exchange core and the polymer spacer where minimal frosting may occur allow the user to use anti-frost liquids such as organic solvent mixture to wipe the frosting. A drain channel is included in the spacer that allows the liquid to flow safely away from electrical connectors. A similar draining channel is also included around electrical connectors and temperature sensors for similar functionality.
7 FIG. 1 FIG. 700 102 702 102 704 706 depicts a mechanical diagramillustrating a cut away side view of another embodiment the lower assemblyofin accordance with some embodiments of the present disclosure. A heat source(e.g., a wave energy heater) is located outside of the vacuum chamber. The lower assemblyincludes a portholeand/or other non-metallic material for heating the matrix vesselvia wave energy if a wave energy heater is used.
8 FIG. 800 802 102 402 102 104 802 depicts a mechanical diagramillustrating another embodiments of the apparatus where a matrix funnelis positioned in the lower assemblyand above the diffusing platein accordance with embodiments of the present disclosure. In this embodiment, the matrix vessel is made of polymer resin and extends from the lower assemblytoward the samples in the upper assembly, leaving a gap at the top for vacuum. The matrix funnelmay be made of a polymer resin, such as Polyamide, Polyimide, PEEK or other insulative high heat plastics material onto which matrix crystals will form less quickly than on colder metal surfaces.
9 FIG.A 9 FIG.C 900 900 902 904 904 202 104 900 904 904 202 906 906 202 902 202 900 902 902 902 202 908 908 902 902 906 906 908 908 900 900 900 902 904 904 202 906 906 202 908 908 902 throughdepict mechanical diagramsA throughC illustrating a sample maskfor securing sample slidesA andB directly to the heat exchange coreof the upper assemblyin accordance with embodiments of the present disclosure. Mechanical diagramA further depicts sample slidesA andB placed against the heat exchange core. In some embodiments, the slide capacity varies between one and four sample slides. Core magnetsA throughD are positioned within the heat exchange coreand are used for securing the sample maskto the heat exchange core. Mechanical diagramB further depicts a top view and a side view of the sample maskfor securing the sample slidesA andB against the heat exchange core. Mask magnetsA throughD are positioned within the sample maskand configured to attract the sample maskto the core magnetsA throughD respectively. Mask magnetsA andB are hidden from view in mechanical diagramsB andC. Mechanical diagramC further depicts a top view and a side view of the magnetic masksecuring the slidesA andB against the heat exchange core. In some embodiments, core magnetsA throughD may be omitted if the heat exchange corecontains ferromagnetic and/or paramagnetic material. In other embodiments, mask magnetsA throughD may be omitted if the sample maskcontains ferromagnetic and/or paramagnetic material. In further embodiments, more or less core magnets and/or mask magnets may be used.
In broader embodiments, an apparatus for providing sublimation is disclosed. The apparatus includes a lower assembly, a top assembly, and a hinge assembly mechanically coupling the lower assembly to the upper assembly. The apparatus is configured for allowing a substrate to be positioned within an interior chamber when in an open position, facilitating deposition of a material onto the substrate via sublimation when in a closed position, and allowing removal of the substrate with the material when returned to the open position.
In some embodiments, the substrate may be used in sample preparation for mass spectrometry imaging.
In some embodiments, the lower assembly may include a vacuum inlet configured for attachment to a vacuum pump.
In some embodiments, the lower assembly may further include a plurality of sensors accessible via an electrical interconnect.
In some embodiments, the lower assembly may further include a heat source electrically coupled via the electrical interconnect.
In some embodiments, the lower assembly may further include a plurality of non-skid feet.
In some embodiments, the upper assembly may be configured to provide an internal chamber when in the closed position and comprises a sample holder.
In some embodiments, the internal chamber may be approximately the shape of a cylinder.
In some embodiments, the internal chamber may be approximately the shape of at least one of a prism, a sphere, and a cone.
In some embodiments, the sample holder may be configured to hold a plurality of slides.
In some embodiments, the samples are secured directly to the heat exchange core without the use of sample holder but with a sample mask or conductive tape.
In some embodiments, the sample mask geometry allows masking of specific areas on the samples including, but not limited to, labels, calibration marks, or reference points.
In some embodiments, the plurality of slides may be one or more metal target plates.
In some embodiments, the sample holder or sample mask may be configured to hold at least one metal target plate.
In some embodiments, the upper assembly may further include a heat exchange core.
In some embodiments, the heat exchange core may be an isolated solid metal block extending from the internal chamber to an exterior of the upper assembly. and acts as a heat sink when cooled with various coolants.
In some embodiments, the heat exchange core may be configured to provide heat sinking from the internal chamber to the exterior of the upper assembly.
In some embodiments, the heat exchange core may be configured to be thermally coupled with a thermoelectric cooler.
In some embodiments, the thermoelectric cooler may be a Peltier cooler.
In some embodiments, the heat exchange core may be configured to be thermally coupled with a liquid coolant (e.g., an ice bath, a dry ice slurry, liquid nitrogen, and/or the like).
In some embodiments, the heat exchange core may be configured to be thermally coupled with a heatsink configured for force air heat transfer.
In some embodiments, the lower assembly may further include a wafer for holding a substance for sublimation.
In some embodiments, the wafer may be a removeable patterned template for holding matrix to be heated via the heat source during sublimation.
In some embodiments, the lower assembly may further include a fixed direct contact plate for holding a substance for sublimation.
In some embodiments, the direct contact plate may be in direct contact with the heat source for holding matrix to be heated via the heat source during sublimation.
In some embodiments, the direct contact plate has a patterned surface or discrete wells to improve even matrix distribution.
In some embodiments, a funnel may be used to direct matrix path from the matrix vessel to the samples.
In some embodiments the funnel may be removeable.
In some embodiments, the funnel may be made of a conductive metal.
In some embodiments, the funnel may be made of a non-conductive material.
In some embodiments, the funnel may be shaped like a cylinder.
In some embodiments, the funnel may be shaped like a cone or prism.
In some embodiments, the heat source may be configured to be electrically coupled to a temperature controller via the electrical interconnect.
In some embodiments, the heat source may be a ceramic heater configured to heat the interior chamber to a temperature of at least 260 degrees Celsius. In further embodiments, the heat source may be a ceramic heater configured to heat the interior chamber to a temperature of at least 300 degrees Celsius.
In some embodiments, the heat source may be configured to achieve a temperature setpoint in less than 120 seconds.
In some embodiments, the heat source may include infrared, induction, and/or resistance heaters.
In some embodiments, the heat source may be an infrared heater positioned outside of the vacuum chamber that transfers heat to the chamber through a non-metallic porthole.
In some embodiments, the upper assembly may further include a handle for configuring the apparatus in the open position or the closed position.
In some embodiments, the hinge assembly may include a motor mechanism for automatically transitioning the apparatus between the open position and the closed position.
In some embodiments, the interior chamber has a volume of less than one liter.
In some embodiments, the interior chamber has a volume less than one liter and a sample capacity of up to four microscope slides.
In some embodiments, the interior chamber may have a volume and may have a sample area at or less than a ratio of 1:7500 liters to square millimeters.
10 FIG. 1000 depicts a flowchartillustrating a method of using the apparatus of using the previously described broader apparatus in accordance with embodiments of the present disclosure.
1002 In step, the method includes configuring the apparatus to be in an open position.
1004 In step, the method further includes positioning a substrate within an interior chamber of the apparatus.
1006 In step, the method further includes configuring the apparatus to be in a closed position with the substrate within the interior chamber.
1008 In step, the method further includes adjusting a pressure and a temperature of the interior chamber for sublimation of a material onto the substrate.
1010 In step, the method further includes configuring the apparatus to be in the open position.
1012 In step, the method further includes removing the substrate from the interior chamber of the apparatus.
11 FIG. 1100 depicts a flowchartillustrating a method for manufacturing the apparatus of the previously described broader apparatus in accordance with embodiments of the present disclosure. The apparatus is configured for allowing a substrate to be positioned within an interior chamber when in an open position, facilitating deposition of a material onto the substrate via sublimation when in a closed position, and allowing removal of the substrate with the material when returned to the open position.
1102 In step, the method includes mechanically assembling a lower assembly.
1104 In step, the method further includes mechanically assembling an upper assembly.
1106 In step, the method further includes mechanically coupling the lower assembly to the upper assembly using a hinge assembly.
In general, the device described herein provides many advantages for sublimation for materials onto a substrate. These include but are not limited to (1) a heater that is positioned within the vacuum and suspended to reduce heat transfer and loss to assembly (2) a ceramic heating capability in excess of 300 degrees, (3) a heat exchange core positioned to insulate the cooling from the rest of the device assembly and compatible with sub-zero coolants (4) a vacuum inlet positioned towards the bottom of the device, and (5) a diffusing plate to distribute vacuum flow as well as retain the heater in position against positioning screws, and (6) a funnel to direct matrix from the heat source to the samples.
While the embodiments have been described in connection with the preferred embodiments of the various figures, it is to be understood that other similar embodiments may be used or modifications and additions may be made to the described embodiment for performing the same function without deviating therefrom. Therefore, the disclosed embodiments should not be limited to any single embodiment, but rather should be construed in breadth and scope in accordance with the appended claims.
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October 23, 2025
April 23, 2026
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